BACKGROUND: To evaluate the efficacy and safety of the first cohort of people in China treated with a responsive neurostimulation system (Epilcure TM , GenLight MedTech, Hangzhou, China) for focal drug-resistant epilepsy in this study. METHODS: This multicenter, before-and-after self-controlled study was conducted across 8 centers from March 2022 to June 2023, involving patients with drug-resistant epilepsy who were undergoing responsive neurostimulation (RNS). The study was based on an ongoing multi-center, single-blind, randomized controlled study. Efficacy was assessed through metrics including median seizure count, seizure frequency reduction (SFR), and response rate. Multivariable linear regression analysis was conducted to explore the relationships of basic clinical factors and intracranial electrophysiological characteristics with SFR. The postoperative quality of life, cognitive function, depression, and anxiety were evaluated as well. RESULTS: The follow-up period for the 19 participants was 10.7 ± 3.4 months. Seizure counts decreased significantly 6 months after device activation, with median SFR of 48% at the 6th month (M6) and 58% at M12 ( P  <0.05). The average response rate after 13 months of treatment was 42%, with 21% ( n  = 4) of the participants achieving seizure freedom. Patients who have previously undergone resective surgery appear to achieve better therapeutic outcomes at M11, M12 and M13 ( β  <0, P  <0.05). No statistically significant differences were observed in patients' scores of quality of life, cognition, depression and anxiety following stimulation when compared to baseline measurements. No serious adverse events related to the devices were observed. CONCLUSIONS: The preliminary findings suggest that Epilcure TM exhibits promising therapeutic potential in reducing the frequency of epileptic seizures. However, to further validate its efficacy, larger-scale randomized controlled trials are required. REGISTRATION Chinese Clinical Trial Registry (No. ChiCTR2200055247).
Humans ; Female ; Male ; Drug Resistant Epilepsy/therapy* ; Adult ; Young Adult ; Middle Aged ; China ; Adolescent ; Treatment Outcome ; Quality of Life ; Single-Blind Method ; Seizures ; Electric Stimulation Therapy/methods*

Objective:To investigate the diagnostic value of cervical cell DNA ploidy analysis combined with negative costimulatory molecule B7 homolog 4 (B7-H4) and protein kinase Cδ (PKCδ) for cervical cancer.Methods:A total of 160 cervical cancer patients diagnosed and treated at Shijiazhuang People's Hospital from January 2018 to January 2022 were selected as the cervical cancer group. Meantime, 160 women who were screened for cervical cancer in our hospital during this period were selected as the control group. According to the examination results, they were divided into normal or inflammatory group ( n=52), low-grade cervical intraepithelial neoplasia (CIN) group ( n=68) and high-grade CIN group ( n=40). The automatic cell image analysis system was used to analyze the DNA ploidy of cervical cells. The levels of B7-H4 and PKCδ in serum were determined by enzyme-linked immunosorbent assay. Pearson method was used to analyze the correlation between serum B7-H4 and PKCδ; the diagnostic value of cervical cell DNA ploidy analysis combined with serum B7-H4 and PKCδ in cervical cancer was evaluated by the receiver operator characteristic (ROC) curve; multivariate logistic regression was used to analyze the risk factors of cervical cancer. Results:The numbers of DNA ploidy positive cases of cervical cells in normal or inflammatory group, low-grade CIN group, high-grade CIN group and cervical cancer group were 16 (30.8%), 27 (39.7%), 26 (65.0%) and 127 (79.4%), respectively, with a statistically significant difference ( H=55.86, P<0.001). Further pin-by-pair comparison showed that compared with normal or inflammatory groups, the proportion of DNA ploidy positive in high-grade CIN group and cervical cancer group were higher (both P<0.05). The proportion of DNA ploidy positive in cervical cancer group was higher than that in low-grade CIN group ( P<0.05). Serum B7-H4 levels in normal or inflammatory group, low-grade CIN group, high-grade CIN group and cervical cancer group were (57.21±10.21), (79.17±11.34), (92.73±15.36), (126.56±20.25) ng/ml, respectively, with a statistically significant difference ( F=285.45, P<0.001). Serum PKCδ levels were (89.34±18.29), (71.79±15.82), (53.39±11.84), (40.23±10.21) ng/ml, respectively, with a statistically significant difference ( F=216.28, P<0.001). Further pin-by-pair comparison showed that serum B7-H4 levels in normal or inflammatory groups, low-grade CIN group, high-grade CIN group and cervical cancer group increased in turn (all P<0.05). Serum PKCδ levels in normal or inflammatory groups, high-grade CIN group and cervical cancer group were decreased in turn (all P<0.05). Pearson correlation analysis showed that the serum B7-H4 and PKCδ levels in patients with cervical cancer were negatively correlated ( r=-0.47, P<0.001). ROC curve analysis showed that the area under the curve (AUC) of cervical cell DNA ploidy for cervical cancer diagnosis was 0.82 (95% CI: 0.78-0.86), and the sensitivity and specificity were 83.9% and 79.9%, respectively. The AUC of serum B7-H4 in the diagnosis of cervical cancer was 0.92 (95% CI: 0.89-0.95), the sensitivity and specificity were 95.7% and 76.1%, respectively, and the cutoff value was 111.12 ng/ml. The AUC of serum PKCδ for diagnosis of cervical cancer was 0.92 (95% CI: 0.89-0.95), the sensitivity and specificity were 85.6% and 88.9%, respectively, and the cut-off value was 54.83 ng/ml. The AUC of the combined diagnosis of cervical cancer was 0.99 (95% CI: 0.97-0.99), and the sensitivity and specificity were 98.3% and 75.9%, respectively. The AUC of the combined diagnosis of cervical cancer was higher than that of DNA ploidy ( Z=8.00, P<0.001), serum B7-H4 ( Z=4.34, P<0.001), and serum PKCδ ( Z=4.61, P<0.001) alone. Multivariate logistic regression analysis showed that high level of B7-H4 in serum ( OR=2.94, 95% CI: 1.78-4.84, P<0.001), low level of PKCδ ( OR=4.33, 95% CI: 1.88-10.00, P=0.001) and positive DNA ploidy in cervical cells ( OR=5.77, 95% CI: 2.38-13.99, P<0.001) were independent risk factors for cervical cancer. Conclusion:The positive proportion of DNA ploidy in cervical cells of patients with cervical cancer is increased, the serum B7-H4 level is increased, the PKCδ level is decreased, and cervical cell DNA ploidy analysis combined with serum B7-H4 and PKCδ has a high diagnostic value for cervical cancer.

The transgender children and adolescents(TCAs)face serious social dilemmas in the process of gender identity and expression,which hinders this group from seeking reasonable and equal rights to survival and development.From the perspective of equal rights and the theoretical framework of social dilemma,by interviewing TCAs who seek help from medical social workers in a hospital's multi-disciplinary transgender clinic,this paper revealed that under the traditional system of"binary gender",TCAs lacked social inclusiveness and infrastructure,which led to the two major social dilemmas of"social traps"and"social barriers"encountered by this group in the process of gender expression and gender identity.Specifically,the social gender selection of TCAs often leads to collective irrational reactions and gender punishment,preventing their legal and effective medical services.To this end,the research team used critical methodology to construct a joint disciplinary diagnosis and treatment path for TCAs with the participation of medical social workers,as well as verified that the path has significant intervention effects in rationalizing the needs of TCAs and their families,alleviating their psychological pressure and social adaptation problems in the process of gender identity,fostering a diverse dialogue environment in their families,as well as enhancing their self-efficacy and social participation,to provide assistahce to the TCAs groups in social difficulties,assisting their rights and interests be included in the child-friendly indicator system,and improving the whole society's tolerance and understanding for TCAs group.

The prognosis for diffusely infiltrating gliomas at World Health Organization (WHO) grade 2-4 remains dismal due to their heterogeneity. The rapid development of genome-wide molecular-profiling-associated studies has greatly promoted the accuracy of glioma classification. Thus, the latest version of the WHO classification of the central nervous system tumors published in 2021 has incorporated more molecular biomarkers together with histological features for the diagnosis of gliomas. Advanced usage of molecular pathology in clinical diagnostic practice provides also new opportunities for the therapy of patients with glioma, including surgery, radiotherapy and chemotherapy, targeted therapy, immunotherapy, and more precision clinical trials. Herein, we highlight the updates in the classification of gliomas according to the latest WHO guidelines and summarize the clinically relevant molecular markers by focusing on their applications in clinical practice. We also review the advances in molecular features of gliomas, which can facilitate the development of glioma therapies, thereby discussing the challenges and future directions of molecular pathology toward precision medicine for patients with glioma.

【Objective】 To investigate the relationship between differential expressions of lncRNAs and mRNAs and Hespintor’s possible anti-tumor mechanism using transcriptome sequencing technology. 【Methods】 First， a nude mouse model of human hepatoma tumors was established. The tumor tissue mass was collected after 4 weeks of group treatment. The cDNA libraries of tumor tissues were established in the Hespintor treatment group and the solvent control group， and transcriptome sequencing was performed. Based on RNA-seq data， the differentially expressed lncRNA and mRNA genes were screened， and the functional enrichment and interaction analysis were performed. The network module division approach was utilized to identify the target genes of Hespintor and build its regulatory network. 【Results】 The Hespintor treatment group yielded a high-confidence differentially expressed gene collection of 2 003 lncRNAs （DEGs lncRNA） and 1 038 mRNAs （DEGs mRNA）. Target mRNAs regulated by DEGs lncRNA were mainly enriched in PIP3 to activate the Akt signal， p53 signal pathway， FOXO-mediated transcription， and cell cycle， among other things. DEGs mRNA were primarily enriched in chemokine signaling pathways， extracellular matrix receptor interactions， complement， and coagulation cascades. Both of them were related in three ways： cell behavior， transcriptional regulation， and cell cycle. 【Conclusion】 The PI3K/Akt signaling pathway may play a key role in the inhibitory effect of Hespintor on tumor， inducing G1/S phase cell cycle arrest and apoptosis.

Objective To explore hemodynamic performance of the aortic dissection after lesions, so as to provide a more scientific basis for patient treatment. Methods Based on computed tomography angiography (CTA) image data from a patient with complex Stanford B-type aortic dissection, the personalized aortic dissection models with different rupture shapes (H-type, O-type, and V-type) at proximal end of the aortic dissection were established. Combined with computational fluid dynamics (CFD) and morphological analysis method, distributions of the velocity at rupture section, the blood flow, the wall pressure and the wall shear stress (WSS) were analyzed. Results The flow velocity, the highest pressure difference and the WSS proportion at entrance of the H-shaped rupture showed larger hemodynamic parameters than those of the other two types. The risk of dissection rupture for type H was the largest, while type V was in the middle, and type O was the smallest. Conclusions This study provides an effective reference for further numerical analysis the cases and formulation of treatment plans.

Objective:To investigate the clinical value of high intensity focused ultrasound (HIFU) ablation combined with levonorgestrel releasing in uterine system (LNG-IUS) in the treatment of adenomyosis.Methods:From January 2015 to January 2018, patients with adenomyosis diagnosed and treated in Obstetrics and Gynecology of our hospital were selected as the research objects. According to the wishes and treatment methods of the patients, the patients were divided into two groups: the combined treatment group was treated with HIFU combined with LNG-IUS, and the HIFU group was only treated with HIFU; the lesion volume and uterine volume reduction rate, hemoglobin, carbohydrate antigen 125 (CA125) and verbal rating scale (VRS) scores were compared between the two groups before and after treatment, and adverse reactions after treatment the scores were recorded.Results:Cases were followed up for 12 months after treatment: the lesion volume reduction rate and uterine volume reduction rate in the combined treatment group were better than those in the HIFU group [(58.8±14.1)% vs (49.3±17.2)%, (37.4±6.2)% vs (32.9±5.0)%, P<0.05]; the hemoglobin level was higher than that in the control group [(113.4±12.8)g/L vs (107.5±10.6)g/L, P<0.05]. In addition, the VRS score of dysmenorrhea in the combined treatment group was also better than that in the HIFU group, with statistically significant difference ( P<0.05). Conclusions:Compared with HIFU ablation alone, patients performed in HIFU combined with LNG-IUS achieved better lesion volume reduction rate and uterine volume reduction rate, and hemoglobin level and dysmenorrhea symptoms improved better in patients with adenomyosis.

Objective: To construct a scientific behavioral research of pasta matrix reaching task (PMRT) and comprehensively evaluate sensory-motor dysfunction caused by brain injury. Methods: Twenty-one SD rats were subjected to 14-days pasta matrix grasping training and then were randomly divided into model group (11 rats) and sham group (6 rats). Motor cortex ischemia was induced by injection of endothelin-1 in SD rats. The number of pasta grabed by the injured forelimb and the location in matrix were evaluated daily 7 days after surgery. The infarct volume was measured by Nissl staining at the 7 days, 14 days, and 28 days after stroke. Results: The number of pasta obtained by rats was reduced from (33.43±1.02) to (20.57±0.57) at 7 days post stroke in model group, and then increased to (26.85±0.98) at 28 days post stroke, although there was a significant difference between sham group(32.33±1.45) and ischemic group (t=3.198, P<0.05). The frequency of retrieval from each slot of the pasta matrix represented that sham group demonstrated a significant gain in performance in the antero quadrant of the matrix compared to ischemic rats by the fourth week after stroke.The stroke volume was decreased from (37.82±1.17)mm³ at 7 days post-stroke to (24.35±0.38)mm³ at 28 days post-stroke, indicating brain recovery from ischemic injury. Conclusion The pasta matrix reaching task can function as a versatile and sensitive behavioral assay that permits experimenters to collect accurate outcome data and manipulate limb use to mimic human clinical phenomena including compensatory strategies and focused rehabilitative training after stroke.

Objective: To estabilsh animal methods of bone-conducted vibration elicited cervical vestibular-evoked myogenic potentials (BCV-cVEMP) and ocular vestibular-evoked myogenic potentials (BCV-oVEMP) in healthy guinea pigs. Methods: Eleven healthy (250-350 g) and awake guinea pigs were selected and undertake conventional BCV-cVEMP and BCV-oVEMP examination in prone position. Parameters of waveforms were cauculated. Results: The BCV-cVEMP and BCV-oVEMP both could be elicited in 100% (22/22) in guinea pigs respectively, threshold was (85.5±10.8)dB SPL and (90.7±10.6)dB SPL for cVEMP and oVEMP; n1 latency was (4.5±1.3)ms and (4.3±1.5)ms for cVEMP and oVEMP; p1 latency was (5.8±1.4)ms and (5.6±1.7)ms respectively; n1-p1 interwave latency was (1.2±0.4)ms for cVEMP and (1.4±0.6)ms for oVEMP, amplitude was (21.5±17.3)μV and (24.0±16.3)μV respectively. Conclusion Both BCV-cVEMP and BCV-oVEMP can be successfully elicited in healthy guinea pigs.

Objective To investigate the mechanism of IL-1β in promoting glial scar formation after spinal cord injury.Methods The experimental model of SCI was created by extradural compression of the spinal cord using an aneurysm clip.Rats were randomly divided into model group, sham operation group, IL-1β inhibitor IL-1RA group, IL-1β group and IL-1β+JAK2-STAT3 inhibitor AG490 group, according to different interventions, then were given normal saline, IL-1RA, IL-1β and IL-1β+AG490 every 10 μL respectively, sham group received only laminectomy.The motion function of the hindlimbs of rats was measured by Basso Beattie Bresnahan(BBB) scores and the expression of GFAP, vimentin and p-STAT3 were detected by Western blot technique, immunofluorescence assay and immunohistochemistry technique at corresponding time points(at the 8th, 12th hour, 1st, 3rd, 7th and 14th day after SCI).Results The expression trend of p-STAT3(at the 8th and 12th hour after SCI),GFAP and vimentin(at the 7th and 14th day after SCI)was: the expressions of p-STAT3, GFAP and vimentin in the model group were significantly higher compared with the sham group(P<0.01), the expression of p-STAT3,GFAP andvimentin in the IL-1RA group were significantly lower compared with the model group(P<0.05) whereas significantly higher compared with the sham group(P<0.05);the expressions of p-STAT3, GFAP and vimentin in the IL-1β+AG490 group were significantly lower compared with the model group(P<0.05)whereas significantly higher compared with the sham group(P<0.05), the expressions of p-STAT3, GFAP and vimentin in the IL-1β group were significantly higher compared with the model group(P<0.05).Conclusions IL-1β can improve glial scar formation via JAK2-STAT3 signal.Inhibition of IL-1β or JAK2-STAT3 can reduce glial scar formation and promote functional recovery of spinal nerve.